Mammalian target of rapamycin (mTOR) is an important signaling transduction molecule that regulates cell growth and proliferation, and is also a protein kinase. It plays an important role mainly by activating ribosomal 40s subunit S6K protein kinase and inhibiting eukaryotic initiation factor 4E (eIF-4E) binding protein 1. The pathway integrates signals from nutrients, energy, and growth factors to regulate a large number of vital process. The abnormal activation of mTOR signaling pathway relates to the occurrence, development and metastasis of tumor.
Rapamycin and its derivatives are mTOR signaling specific inhibitors. At present, the first generation mTOR allosteric inhibitor such as Rapamycin Temsirolimus/Torisel, and Everolimus/Afinitor has been used for the treatment of immune, cardiovascular, malignant tumor and other critical diseases, The mTOR related clinical trials have accumulated to more than 1600 items (clinicaltrials.gov), reflecting a high attention on mTOR pathway in the medicine circles and the drug development circles. However, recent studies have found that human mTOR has at least two functional protein complexes, mTORC1 and mTORC2, which mediate both related and independent physiological and pathological mechanisms. Studies have shown that rapamycin, as an allosteric inhibitor, do not directly target mTORC2, and do not completely block mTORC1 either, therefore, the full therapeutic potential of rapamycin as mTOR targeting drugs cannot be realized.
Substituted pyridine and pyrimidine compounds (Compound A and Compound B) shown in formula A and formula B, as a ATP-competitive selective inhibitor of mTOR shows very good antitumor activity in vivo, good pharmacokinetic properties and good safety, the results of pharmacodynamic study are shown in Chinese patent (201310068888.8), PCT international patent application (PCT/CN2014/072678), and Bioorganic & Medicinal Chemistry Letters 23 (2013) 1212-1216.

However, the methods for preparation the A compound and B compound described in the prior art have many problems, such as low yield, various impurities and unsuitable for industrial production. In summary, a synthetic process of low cost, high purity and suitable for industrial production of substituted pyridine and pyrimidine compound is urgently needed in this field.